rs2717477

Variant names:

• chr12-80378033-G-A
• rs2717477
• NM_001378609.3:c.7047G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-80378033-G-A
• chr12-80378033-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378609.3(OTOGL):​c.7047G>A​(p.Thr2349Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,577,228 control chromosomes in the GnomAD database, including 521,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40882 hom., cov: 31)
  • Exomes 𝑓: 0.82 (481090 hom.)
• Consequence: OTOGL NM_001378609.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.90

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-80378033-G-A is Benign according to our data. Variant chr12-80378033-G-A is described in ClinVar as [Benign]. Clinvar id is 226976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80378033-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.9 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.7047G>A	p.Thr2349Thr	synonymous_variant	Exon 59 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.7047G>A	p.Thr2349Thr	synonymous_variant	Exon 59 of 59	5	NM_001378609.3	ENSP00000447211.2

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108874 AN: 151760 Hom.: 40880 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.758

GnomAD3 exomes AF: 0.769 AC: 152312 AN: 198162 Hom.: 59710 AF XY: 0.783 AC XY: 82601 AN XY: 105560

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.838

Gnomad EAS exome AF: 0.765

Gnomad SAS exome AF: 0.827

Gnomad FIN exome AF: 0.793

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.788

GnomAD4 exome AF: 0.818 AC: 1166610 AN: 1425350 Hom.: 481090 Cov.: 41 AF XY: 0.820 AC XY: 579030 AN XY: 705764

Gnomad4 AFR exome AF: 0.449

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.772

Gnomad4 SAS exome AF: 0.826

Gnomad4 FIN exome AF: 0.799

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.717 AC: 108904 AN: 151878 Hom.: 40882 Cov.: 31 AF XY: 0.718 AC XY: 53281 AN XY: 74236

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.758

Alfa AF: 0.819 Hom.: 117254

Bravo AF: 0.695

Asia WGS AF: 0.782 AC: 2720 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Thr2340Thr in exon 58 of OTOGL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 49.5% (2182/4404) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2717477). -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.013
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2717477; hg19: chr12-80771813; COSMIC: COSV54014294;